title: Arginine methylation of hnRNP A2 does not directly govern its subcellular localization.
abstract: The hnRNP A/B paralogs A1, A2/B1 and A3 are key components of the nuclear 40S hnRNP core particles. Despite a high degree of sequence similarity, increasing evidence suggests they perform additional, functionally distinct roles in RNA metabolism. Here we identify and study the functional consequences of differential post-translational modification of hnRNPs A1, A2 and A3. We show that while arginine residues in the RGG box domain of hnRNP A1 and A3 are almost exhaustively, asymmetrically dimethylated, hnRNP A2 is dimethylated at only a single residue (Arg-254) and this modification is conserved across cell types. It has been suggested that arginine methylation regulates the nucleocytoplasmic distribution of hnRNP A/B proteins. However, we show that transfected cells expressing an A2(R254A) point mutant exhibit no difference in subcellular localization. Similarly, immunostaining and mass spectrometry of endogenous hnRNP A2 in transformed cells reveals a naturally-occurring pool of unmethylated protein but an exclusively nuclear pattern of localization. Our results suggest an alternative role for post-translational arginine methylation of hnRNPs and offer further evidence that the hnRNP A/B paralogs are not functionally redundant.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Lexie R
authors.initials: LR
authors.lastname: Friend
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Landsberg
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Nouwens
authors.forename: Ying
authors.initials: Y
authors.lastname: Wei
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rothnagel
authors.forename: Ross
authors.initials: R
authors.lastname: Smith
mesh_terms: D001120:Arginine / Q000378:metabolism*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D002853:Chromatography, Liquid; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D013058:Mass Spectrometry; D008745:Methylation; D017354:Point Mutation / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics*
chemical_list: D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C439768:hnRNP A2; D001120:Arginine